Anti-adipogenic Action of Pitavastatin Occurs Through the Coordinate Regulation of Ppargamma and Pref-1 Expression.
From: Department of Pathology, Center of Vascular Biology, Weill Medical College of Cornell University, New York, NY 10021, USA.
British journal of pharmacology
- Publish Date: Jul 2007
- ISSN: 0007-1188
- Volume: 151
- Issue: 6
- Pages: 807-15
- Medium: Print
- Language: English
- Citation (JAMA): Nicholson A C, Hajjar D P, Zhou X, et al. Anti-adipogenic Action of Pitavastatin Occurs Through the Coordinate Regulation of Ppargamma and Pref-1 Expression.. Br. J. Pharmacol. Jul 2007;151:807-15
Abstract
Background and purpose:Adipocyte differentiation in vitro is coordinately activated by two transcription factors, peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT enhancer binding protein alpha (C/EBPalpha), but it is inhibited by preadipocyte factor-1 (pref-1). Statins, inhibitors of HMG-CoA reductase and de novo cholesterol synthesis, can have pleiotropic effects which influence adipocyte phenotype by ill-defined mechanisms. We investigated the effects of pitavastatin (NK-104) on adipocyte differentiation and the transcriptional pathways involved.Experimental approach:The effects of pitavastatin on adipocyte differentiation were evaluated by the formation of oil droplets, content of cellular triglyceride and expression of adipocyte-specific genes. Regulatory mechanisms were assessed by analysis of PPARgamma, C/EBPalpha and pref-1 expression.Key results:Pitavastatin significantly inhibited adipocyte differentiation of 3T3-L1 preadipocytes in response to adipogenic inducers. Evidence for inhibition included fewer Oil Red O positive droplets, less cellular triglyceride and decreased expression of adipocyte-specific genes, including fatty acid binding protein (aP2), CD36, adipsin and glucose transporter 4 (GLUT4). The inhibitory effects of pitavastatin on adipocyte differentiation of 3T3-L1 preadipocytes were time and concentration dependent. Pitavastatin significantly blocked induction of PPARgamma expression, but not C/EBPalpha expression or DNA binding activity of PPARgamma. Also, pitavastatin induced pref-1 expression in preadipocytes and maintained expression of pref-1 at high levels in differentiated cells.Conclusions and implications:Our data suggest that pitavastatin inhibits adipocyte differentiation by blocking PPARgamma expression and activating pref-1 expression. These studies may have implications in the regulation of adipogenesis in response to statins.
Mesh Headings (Keywords): 3T3-L1 Cells, Adipocytes, Animals, Azo Compounds, CCAAT-Enhancer-Binding Protein-alpha, Cell Differentiation, DNA, Dose-Response Relationship, Drug, Enzyme Inhibitors, Gene Expression Regulation, Intercellular Signaling Peptides and Proteins, Mice, PPAR gamma, Quinolines, Transcription, Genetic, Triglycerides
Check for Full Text / PubMed Unique Identifier (PMID): 17549051
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.